Phyllanthostatin A

Abstract

An unusal cytostatic (PS ED50 4 ug/ml) lignan ester has been isolated from the Central American tree Phyllanthus acuminatus and is herein designated Phyllanthostatin A. Separation of a methanol extract of the root by size exclusion chromatography, high speed countercurrent distribution and semi-preparative hplc afforded glycoside in 0.007% yield. In solution, phyllanthostatin A was slowly transformed into justicidin-B. The structure of the lignan glycoside, determined by hrfabms and 2D nmr spectroscopy, is: <IMAGE>

Accordingly, what is claimed is: 
     
       1. A lignan glycoside derived from P. acuminatus and having the structural formula: ##STR4## 
     
     
       2. A lignan glycoside which, when placed as a 50 mg sample in CDCL 3 , provides the following  13  C nmr and heteronuclear correlation results:   ______________________________________                                    
              one-bond .sup.1 H, .sup.13 C-                               
                            long-range .sup.1 H,                          
Chemical shift.sup.b                                                      
              correlation.sup.c                                           
                            .sup.13 C correlation.sup.d                   
______________________________________                                    
1   137.31/137.16 (2xs)         H-2', H-6', H-8                           
2   128.59/128.39 (2xs)         H-4, H-11                                 
3   127.70/127.60 (2xs)         H-11                                      
4   126.92 (d)    7.54          H-5, H-11                                 
5   106.37 (d)    7.06          H-4                                       
6   150.63 (s)                  H-8, H-17                                 
7   150.35 (s)                  H-5, H-16                                 
8   105.45/105.35 (2xd)                                                   
                  6.88.sup.e                                              
9   127.70/127.60 (2xs)         H-4, H-5                                  
10  129.70 (s)                  H-8                                       
11   65.26 (t)    5.25, 5.12                                              
12  172.92 (s)                  H-13                                      
13   21.00 (q)    1.99                                                    
14  167.42 (s)                  H-1', H-4.sup.f                           
15  101.28 (t)    5.98, 5.91                                              
16   55.79 (q)    3.71                                                    
17   55.94 (q)    4.00                                                    
1'  131.17/131.10 (2xs)         H-5'                                      
2'  110.84/110.56 (2Xd)                                                   
                  6.83.sup.e    H-6'                                      
3'  147.58-147.31 (2xs).sup.i                                             
                  H-5', H-15                                              
4'  147.58-147.31 (2xs).sup.i   H-2', H-15                                
5'  108.31/108.15 (2xd)                                                   
                  6.90.sup.e                                              
6'  123.86/123.71 (2xd)                                                   
                  6.80.sup.e    H-2'                                      
1"   94.37 (d)    5.52                                                    
2"   72.43 (d).sup.g                                                      
                  3.44                                                    
3"   76.42 (d).sup.g,h                                                    
                  3.38                                                    
4"   69.20 (d).sup.g                                                      
                  3.54                                                    
5|                                                               
     76.32 (d).sup.g,h                                                    
                  3.58                                                    
6"   61.34 (d).sup.g                                                      
                  3.73                                                    
______________________________________                                    
 .sup.b in ppm downfield to TMS; multiplicities by APT experiments;       
 .sup.c one-bond correlations observed in the 1.sub.H 13.sub.c -COSY      
 spectrum;                                                                
 .sup.d long-range couplings through two, three and four bonds observed in
 a .sup.1 H, .sup.13 CCOLOC experiment optimized for J.sub.CH = 5 Hz;     
 .sup.e correlation peak doubled;                                         
 .sup.f correlation peak of low intensity;                                
 .sup.g signals split by ≦0.08 ppm;                                
 .sup.h assignment may be reversed; and                                   
 .sup.i overlapping signals.                                              
     
     
     
       3. A method of inhibiting cell growth in NCI P388 murine lymphocytic leukemia comprising treating said leukemia with a cell growth inhibiting amount of phyllanthostatin A. 
     
     
       4. A method of inhibiting cell growth in a host afflicted with a neoplastic disease correlatable to P388 murine lymphocytic leukemia comprising administering to said host a cell growth inhibiting amount of phyllanthostatin A.